This invention relates to chemical compounds which inhibit Acyl-Coenzyme A: Cholesterol-Acyl Transferase (ACAT). Compounds which possess that property are useful in reducing cholesterol absorption and in the treatment of atherosclerosis.
Atherosclerosis is the most common form of arteriosclerosis and is characterized by the build-up of phospholipids and esterified cholesterol in large and medium arteries causing them to be inelastic and thus weakened. These inelastic and occluded arteries are the most common cause of ischemic heart disease.
ACAT is an important enzyme for the intracellular esterification of cholesterol. Studies of this enzyme in cultured cells (M.S. Brown, J. Biol. Chem. 1980, 617, 458) has shown that increases in ACAT activity represent increases in the presence of cholesterol laden lipoproteins. Regulation of ACAT may be used to help prevent the absorption of cholesterol in the intestinal mucosa, and assist in the reversal of already present atherosclerotic lesions.